(Music - Alexander Borodin, Polovtsian Dances, right click to open in new tab)
I noted in my last post that somewhere between 1966 and the early 1990s, it became very unfashionable for medical professionals to endorse the idea of "hypoglycemia," outside of a super low measured blood glucose level of around 40 or less. "Relative (or reactive) hypoglycemia" had been consigned to a psychosomatic diagnosis. So my relative hypoglycemia which predictably occurred at expected physiologic intervals after ingestion of exclusively high-sugar foods or drinks must have been all in my head. :-) In fact, the year before I was born, the American Diabetes Association, the Endocrine Society, and the American Medical Association issued a joint statement on hypoglycemia, stating that widespread publicity "has led the public to believe that there is a widespread and unrecognized occurrence of hypoglycemia in this country� These claims are not supported by the medical evidence." The American Dietetic Association stated: "Valid evidence is lacking to support the hypothesis that reactive hypoglycemia is common cause of violent behavior."
However, when blood glucose falls to quite low levels, the body does tend to react rather aggressively in order to prevent death. Stress hormones, including catecholamines and glucocorticoids, growth hormone, and glucagon are all released. This high-powered combo would no doubt cause sweating, palpitations, anxiety, weakness, crankiness, and other symptoms traditionally associated with hypoglycemia (but can also occur whenever high levels of these hormones are released for any cause) (1 - amazing paper, by the way. I highly recommend it). If the blood glucose falls low enough that the brain is impaired, certainly very bizarre behavior (such as psychosis) can be observed.
How common is such low glucose outside very rare insulin-producing tumors or accidental overdoses of diabetic medications? Well, actually, in oral glucose tolerance tests (the gold standard is when you are given 50 grams of dextrose after an overnight fast, and then blood glucose is measured continuously for up to six hours - often the absolute nadir is missed if the glucose is not measured continuously, but rather at half hour intervals, as is also common), there is a wide range of glucose nadirs in the blood levels of those tested. The average level is about 65, but 10% of people fell below 47, with 2.5% of people below 39. That means that 1 in 40 people could expect to have "true" hypoglycemia in the context of a pure carbohydrate snack after a fast. This effect can be accentuated by caffeine and alcohol.
However, when one goes around measuring glucose levels of typical human beings eating mixed meals (not participating in oral glucose tolerance tests) levels almost never fell below 70. In these healthy subjects, levels pretty much stayed between 70-100 all day long, before and after meals, and overnight. It was a combination of these findings and studies of so-called hypoglycemics whose blood glucose levels did not correlate to symptoms that consigned "relative" or "reactive" hypoglycemia to conservative medical never-never land. However, in my own case, the symptoms were predictable, and the predictable treatment of switching to a higher-protein, higher-fat, less crappy diet cured it, which I would find odd if it were entirely psychosomatic. Also interesting and pointing to a physiologic cause is that the symptoms returned for me during pregnancy - where insulin reactions and "relative" hypoglycemia will tend to be of larger magnitude than in the non-gravid state, in order to promote glucose uptake by the growing fetus.
But there are other very interesting correlates between hypoglycemia and behavior and mood. A researcher named Bolton studied the Peruvian Quolla Indians, who are apparently known as "perhaps the meanest and most unlikeable people on earth." (2) These people, particularly the men, seemed to act out in irrational acts of violence, and also seemed to have very strong sugar cravings. Bolton happened to do glucose tolerance tests in many of the men, and he noticed a statistically significant correlation between the most aggressive subjects and those who had the lowest blood glucose values during the GTT (3). Another researcher, Virkkunen, studied men who had committed serious violent assaults. Their GTTs were also remarkable for higher peak glucose values and subsequently lower glucose nadirs than controls (4). Folks with antisocial personalities have also been noted to have low blood glucose levels, and, once again, it is important to note that many of these men perpetrated the crimes under the influence of alcohol, which will accentuate the hypoglycemic effect. Similar studies in the general population show that both men and women whose blood glucose fall more rapidly during a glucose tolerance test will tend to have higher ratings of aggression (5)(6). In these studies, a glucose level of 63 or lower was strongly associated with the aggressive tendencies. This is still outside a normal healthy humans' blood glucose range eating normal food, but much, much closer to the normal range than 40.
Wow. I guess rapidly fluctuating blood glucose does cause behavioral changes� wait a minute, there, buckaroos - as I had noticed in my perusal of the rather badly reasoned behavior/blood glucose/insulin resistance literature (which I will go over in the next post), and which Inthewooo noted in her comment on the first post in this series, these are mere correlations. Why is the blood glucose changing more rapidly in certain people than others to the same food or glucose stimuli? Could an underlying mechanism explain both aggression and hypoglycemia?
Virkkunen's more violent reactive hypoglycemics had enhanced insulin response to the oral GGT. And it has been found that impulsive offenders who act aggressively, particularly when intoxicated, have lower levels of serotonin turnover (measured low levels of the metabolite of the serotonin metabolite 5-HIAA in the CSF (7)). Low levels of brain serotonin are associated with enhanced insulin secretion and a tendency to develop low blood glucose levels. The data is a bit tenuous, but at least this mechanism makes some sense in the big picture.
Next up - carb craving and chocolate and PMS and Wurtman's rodents! Women with PCOS, reactive hypoglycemia, hyperglycemia, and mood relationships. You might be surprised at what the science shows...
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